Berberine, an isoquinoline alkaloid suppresses TXNIP mediated NLRP3 inflammasome activation in MSU crystal stimulated RAW 264.7 macrophages through the upregulation of Nrf2 transcription factor and alleviates MSU crystal induced inflammation in rats

Dinesh, Palani; Rasool, Mahaboobkhan

doi:10.1016/j.intimp.2016.12.031

Cited by 104 publications

(65 citation statements)

References 38 publications

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“…6), suggesting that berberine is a strong Nrf2 activator. Previous studies also demonstrated the ability of berberine to activate Nrf2 nuclear translocation and promote its protective effects in different disease models (Zhang et al, 2016;Dinesh and Rasool, 2017;Mahmoud et al, 2017). These results suggest that the P-gp induction by berberine is achieved through activation of Nrf2.…”

Section: Discussionsupporting

confidence: 56%

Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms

Jing

Safarpour

Zhang

et al. 2018

J Pharmacol Exp Ther

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Downregulation of P-glycoprotein (P-gp) is implicated in the pathophysiology of inflammatory bowel disease (IBD). Berberine, a principal isoquinoline alkaloid extracted from species, has been reported to exhibit therapeutic potential in IBD. In this study, we used a dextran sulfate sodium (DSS)-induced colitis rat model to evaluate the effect of berberine on P-gp and explore its mechanism of action. Berberine treatment improved DSS-induced colitis symptoms, attenuated inflammatory markers (myeloperoxidase, tumor necrosis factor-, and interleukin-1 and -6), and enhanced P-gp expression in a dose-dependent manner. Although colonic expression of the P-gp-related nuclear receptor pregnane X receptor and transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) were downregulated in the colitis model, gene and protein expression analysis revealed that berberine treatment reversed only the downregulation of Nrf2. In vitro studies using Caco-2 cells showed that the multidrug resistance 1 () gene and P-gp protein were upregulated by berberine in a dose- and time-dependent manner. Significant upregulation of the gene by berberine was abrogated by Nrf2 silencing, indicating that the Nrf2-mediated pathway was responsible for this activation. Luciferase assays showed a dose-dependent increase in Nrf2 reporter gene activity after berberine treatment in Caco-2 cells, with a significant 2-fold elevation at 2.5M berberine, suggesting that berberine is a strong Nrf2 activator. These results indicate the possible involvement of Nrf2-mediated upregulation of P-gp in the therapeutic effect of berberine on colitis and highlight the potential of P-gp and/or Nrf2 as new therapeutic targets for IBD.

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Section: Discussionsupporting

confidence: 56%

Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms

Jing

Safarpour

Zhang

et al. 2018

J Pharmacol Exp Ther

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“…Macrophages, along with other immune cells, such as neutrophils, play a vital role in mediating joint inflammation in gout. 17,[21][22][23] Stimulating with MSU, the macrophages can release IL-1β, a cytokine crucial to initiate out pathogenesis and neutrophil recruitment. 24 Mature and functional IL-1β is The protein expressions of NLRP3, procaspase-1, caspase-1, pro-IL-1β, and IL-1β were evaluated in the whole cell lysates.…”

Section: Discussionmentioning

confidence: 99%

“…17 Briefly, rats were randomly divided into the following six groups, each containing eight animals: normal control group, MSU (model) group, MSU+colchicine (Col: 0.28 mg/kg, once a day) group, MSU+curcumin (100 mg/kg, once a day) group, MSU+curcumin (150 mg/kg, once a day) group, and MSU +curcumin (200 mg/kg, once a day) group. 17 Briefly, rats were randomly divided into the following six groups, each containing eight animals: normal control group, MSU (model) group, MSU+colchicine (Col: 0.28 mg/kg, once a day) group, MSU+curcumin (100 mg/kg, once a day) group, MSU+curcumin (150 mg/kg, once a day) group, and MSU +curcumin (200 mg/kg, once a day) group.…”

Section: Msu-induced Gouty Arthritis Modelmentioning

confidence: 99%

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Curcumin ameliorates monosodium urate‐induced gouty arthritis through Nod‐like receptor 3 inflammasome mediation via inhibiting nuclear factor‐kappa B signaling

Sun

et al. 2018

J of Cellular Biochemistry

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Background Monosodium urate (MSU) crystals‐induced inflammation is a key initiator in gouty arthritis. Curcumin is an active ingredient possessing anti‐inflammatory efficacy. But the underlying mechanism is not fully understood and its effect on gouty arthritis remains elusive. Methods We evaluated the effects of curcumin on cell viability in primary rat abdominal macrophages with 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT). Then supernatants of MSU crystals–stimulated cells were collected and subjected to enzyme‐linked immunosorbent assay for checking the modulation of curcumin on interleukin (IL)‐1β and tumor necrosis factor (TNF)‐α. Meanwhile, cells were analyzed by using Western blot analysis and quantitative polymerase chain reaction (QPCR) to investigate the effects of curcumin on Nod‐like receptor 3 (NLRP3) inflammasome/nuclear factor‐kappa B (NF‐κB) signaling. We also investigated the in vivo efficacy of curcumin with MSU‐induced gouty arthritis rat models. Results Curcumin could reduce MSU crystals‐induced IL‐1β and TNF‐α in vitro. Western blot analysis and QPCR results revealed that curcumin regulated the production of these cytokines by suppressing the expression of inflammasome key components, including NLRP3, caspase‐1. Further studies showed that the suppressive efficacy of curcumin on inflammasome was mediated by inhibiting MSU‐induced NF‐κB signaling activation. Intraperitoneal administration of curcumin could ameliorate symptoms of MSU‐induced gouty arthritis, including the joint circumference, infiltration of neutrophils in knee joints, and production of IL‐1β, TNF‐α, and elastase. Western blot analysis revealed that the levels of NLRP3, procaspase‐1, caspase‐1, pro‐IL‐1β, and IL‐1β were downregulated by curcumin in vivo. Conclusions These results indicated that curcumin could effectively ameliorate MSU crystal‐induced gouty arthritis through NLRP3 inflammasome mediation via inhibiting NF‐κB signaling both in vitro and in vivo, suggesting a promising active ingredient for the prevention and treatment of gouty arthritis.

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“…Therefore, it will be meaningful to evaluate coptisine's effect on cellular senescence of cancer cells. Another essential issue which needs to be further detected in future investigation is the role of coptisine to act as small‐molecule inhibitor of key markers involved in inflammation, CVDs, etc Berberine is revealed to diminish mRNA overexpression of caspase‐1 and NLRP3 in MSU‐challenged Raw 264.7 cells, and it also regulates pyroptosis in human hepatocellular carcinoma . Since caspase‐1 is a key marker participating in inflammasome assembling and pyroptosis occurrence, and coptisine displays considerable suppressing effect on NLRP3 inflammasome priming and assembly, another relevant subject for further study can be the role of coptisine as small‐molecular inhibitor of caspase‐1 and the downstream pyroptosis activation.…”

Section: Future Prospectsmentioning

confidence: 99%

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

Luo

Deng

et al. 2019

J Cellular Molecular Medi

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Coptisine is a natural small‐molecular compound extracted from Coptis chinensis (CC) with a history of using for thousands of years. This work aimed at summarizing coptisine's activity and providing advice for its clinical use. We analysed the online papers in the database of SciFinder, Web of Science, PubMed, Google scholar and CNKI by setting keywords as ‘coptisine’ in combination of ‘each pivotal pathway target’. Based on the existing literatures, we find (a) coptisine exerted potential to be an anti‐cancer, anti‐inflammatory, CAD ameliorating or anti‐bacterial drug through regulating the signalling transduction of pathways such as NF‐κB, MAPK, PI3K/Akt, NLRP3 inflammasome, RANKL/RANK and Beclin 1/Sirt1. However, we also (b) observe that the plasma concentration of coptisine demonstrates obvious non‐liner relationship with dosage, and even the highest dosage used in animal study actually cannot reach the minimum concentration level used in cell experiments owing to the poor absorption and low availability of coptisine. We conclude (a) further investigations can focus on coptisine's effect on caspase‐1‐involved inflammasome assembling and pyroptosis activation, as well as autophagy. (b) Under circumstance of promoting coptisine availability by pursuing nano‐ or microrods strategies or applying salt‐forming process to coptisine, can it be introduced to clinical trial.

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Berberine, an isoquinoline alkaloid suppresses TXNIP mediated NLRP3 inflammasome activation in MSU crystal stimulated RAW 264.7 macrophages through the upregulation of Nrf2 transcription factor and alleviates MSU crystal induced inflammation in rats

Cited by 104 publications

References 38 publications

Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms

Berberine Upregulates P-Glycoprotein in Human Caco-2 Cells and in an Experimental Model of Colitis in the Rat via Activation of Nrf2-Dependent Mechanisms

Curcumin ameliorates monosodium urate‐induced gouty arthritis through Nod‐like receptor 3 inflammasome mediation via inhibiting nuclear factor‐kappa B signaling

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

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